Bryostatin-1 is an anticancer agent that has undergone both laboratory and human trials. In the laboratory it has been shown to inhibit the growth of melanoma tumors in mice. In phase I human trials in the patients tested that had melanoma, it has been shown to cause a partial remission in 3/8 patients. We have designed a clinical protocol to test this agent in humans that have metastatic melanoma. In addition to looking for a clinical response, we are also examining the patient's biologic response to this agent and the pharmacology of bryostatin-1 in these patients. The patients receive their first infusion of bryostatin-1 in the GCRC. During and after the infusion, blood samples are drawn at specific time intervals and test are done to examine the effects of bryostatin-1 on platelet and white cell function. Blood samples are analyzed for drug levels. Twenty-four hours after the infusion the patient's tumor is biopsied to examine the biologic response. Patients return to the outpatient GCRC on a weekly basis to get a one-hour infusion of bryostatin-1. At this time they are examined fully to determine the toxicity and response to treatment. Although only 7 patients have so far been entered on this protocol, we have been able to demonstrate that bryostatin-1 is non-toxic at the doses being administered. There have been no grade 2 toxicities. Grade 1 toxicity has been limited to headaches and muscle pains. There has been no hair loss, nausea and vomiting, or effects on the WBC or RBC counts. Laboratory tests have demonstrated "priming" of neutrophils during the bryostatin-1 infusion and activation of protein kinase C. There have been two patients that have progressed while on therapy and there is one patient with stable disease and one patient with minimal response. Our goal is to enter 14 patients into this protocol.